http://www.sciencedirect.com/science?_ob=ArticleURL_udi=B6T1B-4YMWCMP-16_user=10_coverDate=03%2F26%2F2010_rdoc=1_fmt=high_orig=search_origin=search_sort=d_docanchor=view=c_acct=C000050221_version=1_urlVersion=0_userid=10md5=2e629a5430d886353a900e35e59f27d7searchtype=a Volume 375, Issue 9719 , 20 March 2010-26 March 2010, Pages 1030-1047 doi:10.1016/S0140-6736(10)60353-4 | How to Cite or Link Using DOI Copyright 2010 Elsevier Ltd All rights reserved. Cited By in Scopus (2) Permissions Reprints Seminar Colorectal cancer This article is not included in your organization's subscription. However, you may be able to access this article under your organization's agreement with Elsevier. Prof David Cunningham MD a , , , Prof Wendy Atkin PhD b , Prof Heinz-Josef Lenz MD c , Prof Henry T Lynch MD d , Prof Bruce Minsky MD e , Prof Bernard Nordlinger MD f and Naureen Starling MRCP a a Gastrointestinal Unit, Royal Marsden Hospital National Health Service Foundation Trust, London and Surrey, UK b Department of Surgery and Cancer, Imperial College, London, UK c Sharon Carpenter Laboratory, University of Southern California/Norris Comprehensive Cancer Center, Keck School of Medicine, Los Angeles, CA, USA d Department of Preventive Medicine and Public Health, Creighton University School of Medicine, Omaha, NE, USA e University of Chicago Medical Centre, Chicago, IL, USA f Service de Chirurgie Gnrale et Digestive, Hpital Ambroise Par, Boulogne, France Available online 18 March 2010. Summary Substantial progress has been made in colorectal cancer in the past decade. Screening, used to identify individuals at an early stage, has improved outcome. There is greater understanding of the genetic basis of inherited colorectal cancer and identification of patients at risk. Optimisation of surgery for patients with localised disease has had a major effect on survival at 5 years and 10 years. For rectal cancer, identification of patients at greatest risk of local failure is important in the selection of patients for preoperative chemoradiation, a strategy proven to improve outcomes in these patients. Stringent postoperative follow-up helps the early identification of potentially radically treatable oligometastatic disease and improves long-term survival. Treatment with adjuvant fluoropyrimidine for colon and rectal cancers further improves survival, more so in stage III than in stage II disease, and oxaliplatin-based combination chemotherapy is now routinely used for stage III disease, although efficacy must be carefully balanced against toxicity. In stage II disease, molecular markers such as microsatellite instability might help select patients for treatment. The integration of targeted treatments with conventional cytotoxic drugs has expanded the treatment of metastatic disease resulting in incremental survival gains. However, biomarker development is essential to aid selection of patients likely to respond to therapy, thereby rationalising treatments and improving outcomes. Article Outline Introduction Molecular carcinogenesis Epidemiology Risk factors Genetic epidemiology: Lynch syndrome as model Screening of colorectal cancer Diagnosis and staging Surgery Radiation treatment for rectal cancer Adjuvant treatment for early stage disease Treatment of metastatic disease Prognostic and predictive molecular markers Conclusions Search strategy and selection criteria Acknowledgements References Figure.High-resolution MRI of rectal cancer Red arrow shows T2 (tumour invading muscularis propria) rectal tumour; white arrow shows lymph node in the mesorectum; and yellow dotted line shows the rectal fascia. View Within Article http://www.gopubmed.org/web/gopubmed/1?WEB0x17xezfnrs17I7I1I00h001000j100200010 100,000 of 129,713 documents semantically analyzed 1 2 Top Years Publications 2009 7,184 2008 6,991 2007 6,761 2006 6,273 2005 6,121 2004 5,672 2003 5,204 2010 5,128 2002 4,994 2001 4,549 2000 4,440 1999 4,212 1998 3,908 1997 3,541 1996 3,511 1995 3,390 1994 3,162 1993 2,991 1992 2,936 1991 2,623 1 2 1 2 3 ... 9 Top Countries Publications USA 25,177 Japan 11,190 United Kingdom 7,076 Germany 6,097 Italy 5,342 France 4,470 China 3,233 Netherlands 2,647 Canada 2,115 Australia 1,937 Spain 1,862 South Korea 1,573 Sweden 1,570 Switzerland 1,024 Denmark 931 Taiwan 918 Israel 872 Greece 747 Norway 742 Belgium 723 1 2 3 ... 9 1 2 3 ... 132 Top Cities Publications Tokyo 2,450 New York City 1,995 London 1,608 Boston 1,500 Houston 1,310 Bethesda 1,018 Paris 1,012 Rome 1,000 Philadelphia 948 Seoul, South Korea 904 Baltimore 898 Milan 720 Heidelberg 704 Berlin, Germany 683 Toronto 676 Amsterdam 663 Los Angeles 656 Osaka 645 Rochester, MN, USA 628 Cleveland 625 1 2 3 ... 132 1 2 3 ... 182 Top Journals Publications Cancer Res 2,521 Dis Colon Rectum 2,393 Int J Cancer 1,734 Gan To Kagaku Ryoho 1,552 Br J Cancer 1,494 Anticancer Res 1,389 Cancer 1,323 J Clin Oncol 1,137 Br J Surg 1,125 Gastroenterology 1,111 Clin Cancer Res 1,071 Int J Colorectal Dis 910 Eur J Cancer 886 World J Gastroenterol 839 Am J Gastroenterol 833 Gut 822 J Natl Cancer Inst 765 Cancer Epidemiol Biomarkers Prev 758 Cancer Lett 737 Hepatogastroenterology 730 1 2 3 ... 182 1 2 3 ... 1735 Top Terms Publications Humans 91,564 Colorectal Neoplasms 54,618 Patients 47,789 Neoplasms 38,226 Middle Aged 37,147 Colonic Neoplasms 36,667 Aged 33,258 Adult 26,376 Carcinoma 25,709 Adenocarcinoma 18,010 Evaluation Studies as Topic 17,868 Neoplasm Metastasis 17,110 Rectal Neoplasms 16,365 Animals 14,981 Genes 14,451 Aged, 80 and over 13,579 Surgery 12,682 Proteins 12,618 Diagnosis 12,511 Tissues 11,828 1 2 3 ... 1735
热门论文全文见 http://www.sciencedirect.com/science?_ob=ArticleURL_udi=B6T1B-4YNN0BH-1_user=9230734_coverDate=04%2F09%2F2010_rdoc=1_fmt=high_orig=search_origin=search_sort=d_docanchor=view=c_acct=C000059499_version=1_urlVersion=0_userid=9230734md5=4ce1ebfb981a2d4f18ede29b91a480c8searchtype=a Volume 375, Issue 9721 , 3 April 2010-9 April 2010, Pages 1212-1223 doi:10.1016/S0140-6736(10)60096-7 | How to Cite or Link Using DOI Copyright 2010 Elsevier Ltd All rights reserved. Cited By in Scopus (2) Permissions Reprints New Drug Class New antiarrhythmic drugs for treatment of atrial fibrillation Prof Dobromir Dobrev MD a , , and Prof Stanley Nattel MD b a Department of Pharmacology and Toxicology, Dresden University of Technology, Dresden, Germany b Department of Medicine and Research Center, Montreal Heart Institute and Universit de Montral and Department of Pharmacology and Therapeutics, McGill University, Montreal, QC, Canada http://www.gopubmed.org/web/gopubmed/1?WEB0qtx7crbpeou0IhI1I00h001000j100200010 atrial fibrillation and Amiodarone and Dronedarone 108 documents semantically analyzed Top Years Publications 2010 31 2009 25 2008 14 2007 11 2006 7 2005 7 2004 6 2001 2 2003 2 2000 2 2002 1 Top Countries Publications USA 36 Germany 17 France 11 United Kingdom 5 Denmark 3 Canada 2 Italy 2 Netherlands 1 Turkey 1 Poland 1 Brazil 1 New Zealand 1 Hungary 1 1 2 3 Top Cities Publications Frankfurt 9 Los Angeles 5 Penn Hills 4 Copenhagen 3 Paris 3 London 3 Montpellier 3 Boston 2 Hartford 2 Castres 2 Lyon 2 San Antonio 1 Rotterdam 1 Pittsburgh 1 Framingham 1 Utica 1 Toronto 1 Brescia 1 Dresden 1 Minden 1 1 2 3 1 2 3 4 Top Journals Publications N Engl J Med 11 J Cardiovasc Electrophysiol 5 J Am Coll Cardiol 5 Dtsch Med Wochenschr 5 Curr Opin Cardiol 4 J Cardiovasc Pharmacol Ther 3 Kardiologiia 3 J Cardiovasc Pharmacol 3 Vasc Health Risk Manag 2 Ann Pharmacother 2 Expert Opin Drug Saf 2 Nat Rev Drug Discov 2 Circulation 2 Expert Rev Cardiovasc Ther 2 Europace 2 Am J Cardiol 2 Am Heart J 2 J Interv Card Electrophysiol 2 Arch Mal Coeur Vaiss 2 Pharmacotherapy 1 1 2 3 4 1 2 3 ... 26 Top Terms Publications Atrial Fibrillation 108 Amiodarone 108 Anti-Arrhythmia Agents 99 fibril 94 Humans 93 Patients 67 Pharmaceutical Preparations 63 Recurrence 41 Mortality 36 Arrhythmias, Cardiac 35 Safety 34 Atrial Flutter 31 Heart Failure 28 Maintenance 27 Treatment Outcome 27 Heart Rate 26 Hospitalization 25 Clinical Trials as Topic 23 Evaluation Studies as Topic 22 Animals 22 1 2 3 ... 26 1 2 3 ... 14 Top Authors Publications Hohnloser S 7 Crijns H 3 Torp-Pedersen C 2 Santini M 2 Cook G 2 Nattel S 2 Kowey P 2 Preobrazhenski? D 2 Connolly S 2 Capucci A 2 Naccarelli G 2 Wolbrette D 2 Samii S 2 Legrand B 2 Nisato D 2 Gautier P 2 Kber L 1 Christiansen C 1 Davy J 1 LE Heuzey J 1 1 2 3 ... 14
http://www.sciencedirect.com/science?_ob=ArticleURL_udi=B6T1B-4YYD7BT-2_user=9230734_coverDate=05%2F14%2F2010_rdoc=1_fmt=high_orig=search_origin=search_sort=d_docanchor=view=c_acct=C000059499_version=1_urlVersion=0_userid=9230734md5=f3c7d17c1c912957a6ae216db4153b1csearchtype=a Volume 375, Issue 9726 , 8 May 2010-14 May 2010, Pages 1624-1633 doi:10.1016/S0140-6736(10)60551-X | How to Cite or Link Using DOI Copyright 2010 Elsevier Ltd All rights reserved. Cited By in Scopus (6) Permissions Reprints Fast track Articles Once-only flexible sigmoidoscopy screening in prevention of colorectal cancer : a multicentre randomised controlled trial Prof Wendy S Atkin PhD a , , , Rob Edwards PhD b , Ines Kralj-Hans PhD a , Kate Wooldrage MSc a , Andrew R Hart MD c , Prof John MA Northover MS d , D Max Parkin MD e , Prof Jane Wardle PhD f , Prof Stephen W Duffy MSc b , Prof Jack Cuzick PhD b and UK Flexible Sigmoidoscopy Trial Investigators a Department of Surgery and Cancer, Imperial College London, London, UK b Cancer Research UK Centre for Epidemiology, Mathematics and Statistics, Wolfson Institute of Preventive Medicine, Queen Mary University of London, London, UK c School of Medicine, Health Policy and Practice, University of East Anglia, Norwich, UK d Department of Surgery, St Mark's Hospital, Harrow, Middlesex, UK e Clinical Trials Service Unit and Epidemiological Studies Unit, University of Oxford, Oxford, UK f Health Behaviour Research Centre, Department of Epidemiology and Public Health, University College London, London, UK Available online 27 April 2010. Refersto: Can endoscopy protect against colorectal cancer? An RCT The Lancet , Volume 375, Issue 9726 , 8 May 2010-14 May 2010 , Pages 1582-1584 , David F Ransohoff PDF (197 K) | Referredtoby: Can endoscopy protect against colorectal cancer? An RCT The Lancet , Volume 375, Issue 9726 , 8 May 2010-14 May 2010 , Pages 1582-1584 , David F Ransohoff PDF (197 K) | http://www.gopubmed.org/web/gopubmed/1?WEB1mOWEB10O00d000j10020001000h00100090000 flexible sigmoidoscopy and screening and prevention and colorectal cancer 315 documents semantically analyzed 1 2 Top Years Publications 2002 23 2005 21 2003 20 1999 19 2000 19 2001 19 1998 17 2004 16 1996 16 2007 13 2006 13 2008 12 1997 12 2009 11 1995 10 1992 10 1993 9 2010 8 1987 8 1994 7 1 2 1 2 Top Countries Publications USA 163 United Kingdom 31 Norway 17 Italy 9 Israel 8 Australia 7 Canada 6 Japan 4 Switzerland 3 Germany 3 Sweden 3 Hong Kong 2 Spain 2 Greece 2 China 2 Denmark 2 Singapore 1 Iran 1 New Zealand 1 Belgium 1 1 2 1 2 3 ... 7 Top Cities Publications London 14 Boston 11 Bethesda 10 Philadelphia 10 Minneapolis 9 Oslo 8 Pittsburgh 6 New York City 6 Atlanta 6 Washington, USA 6 Tel Aviv-Yafo 4 Ann Arbor 4 Houston 4 Cleveland 4 Indianapolis 3 Portland, USA 3 Los Angeles 3 Seattle 3 Oakland 3 Porsgrunn 3 1 2 3 ... 7 1 2 3 ... 7 Top Journals Publications Gut 12 Am J Gastroenterol 12 Gastroenterology 11 Prev Med 10 J Med Screen 9 Cancer 9 Am Fam Physician 8 Scand J Gastroenterol 7 Postgrad Med 7 Endoscopy 6 Ann Intern Med 6 Clin Gastroenterol Hepatol 6 Am J Prev Med 6 Lancet 5 Cancer Epidemiol Biomarkers Prev 5 J Gen Intern Med 5 Med J Aust 5 Cancer Detect Prev 5 Gastrointest Endosc 5 J Fam Pract 5 1 2 3 ... 7 1 2 3 ... 51 Top Terms Publications Sigmoidoscopy 315 Humans 311 Colorectal Neoplasms 290 Mass Screening 252 Middle Aged 205 Occult Blood 179 Colonoscopy 167 Patients 164 Hematologic Tests 160 Aged 149 Mortality 105 Health Planning Guidelines 92 Adenoma 87 Adult 83 Evaluation Studies as Topic 81 Methods 75 Colonic Neoplasms 72 Physicians 67 Incidence 62 Sensitivity and Specificity 58 1 2 3 ... 51 1 2 3 ... 51 Top Authors Publications Hoff G 18 Grotmol T 12 Bretthauer M 12 Wardle J 10 Atkin W 10 Gondal G 8 Hofstad B 7 Thiis-Evensen E 7 Weissfeld J 6 Eide T 6 Levin T 6 Borum M 5 Nadel M 5 McCaffery K 5 Skovlund E 5 Bond J 5 Bresalier R 4 Schn R 4 Hayes R 4 Gohagan J 4 1 2 3 ... 51
两栖动物在疫病影响下的生活史策略及死亡率变化 当前疫病对两栖动物影响的研究，主要集中在感染后的直接代价即致死率方面。但是疫病对两栖动物的影响，有时可能没有这么直接。本文通过野外调查和实验室验证两种方法，比较了被感染蟾蜍在生长发育，存活率方面受的影响，并比较了不同生活史阶段蟾蜍对疫病的反应。结果表明，幼体阶段感染的蟾蜍，它对疾病的反应表现出一种积累的效应，感染的作用会在变态期或变态后表现出来。被感染的幼体在生长方面会付出代价，导致幼体在变态期或变态后的死亡率升高。即使某些个体在死亡时身上都没有表现出被感染的症状，但是这种疫病对它们的影响仍然存在。变态后感染的个体全都有感染症状。我们的研究还表明，疫病对两栖动物生存率的影响会因个体体质和所处的不同生活史阶段有所差异。在全球气候变化的大背景下，许多研究都表明两栖动物会分布到一些并不是它们最适宜的环境中。在这种情况下，类似于疫病这样的环境条件对两栖动物生存影响的研究就显示尤为重要了。 Trenton W.J. et al., Life history tradeoffs influence mortality associated with the amphibian pathogen Batrachochytrium dendrobatidis . Oikos. doi: 10.1111/j.1600-0706.2008.17202.x. 评论 ：今年是蛙年，当前全世界范围内两栖动物数量下降是一个普遍趋势也备受关注，两栖动物保护也是保护生物学研究的热点问题。全球气候变化，人为干扰，外来种入侵，以及疫病等都会导致两栖动物多样性和种群密度下降。本文的研究新意在于，以往研究野生动物流行疫病对两栖动物的影响时，主要着眼点在感染后的致死性方面，认为流行疫病会导致两栖动物大量死亡，因而也被认为是导致其数量下降主要原因之一。这篇文章表明除了致死这种直接作用，疫病还会导致两栖动物的生活史特征发生改变，会影响到其生长发育，并且在变态期这样的生活史敏感时期，还会引起个体死亡。因而在讨论疫病对两栖动物影响时，还不能忽视这种间接的作用。
http://www.sciencenet.cn/htmlnews/2009/9/223497.shtm 樊明文小组防龋DNA疫苗研制获重大突破 我国5岁儿童患龋齿病率为64%，成年人达88%，而老年人几乎为100%！现对这样的现实，能否有一种疫苗让人们不再患龋齿呢？有！ 9月18日，我国著名口腔医学专家、武汉大学口腔医学院名誉院长樊明文教授在新闻发布会上称，经过他与课题组成员20余年的研究，防龋DNA疫苗已取得重大进展。该疫苗将做成喷雾剂，主要用于1-3岁的小孩，喷入鼻腔内，小孩可直接对龋齿产生免疫，从而可望一生告别蛀牙。目前，课题组已联合华中科技大学生命科学院等单位，完成裸疫苗和载体的组装，下一步将完成佐剂的组装。载体和佐剂将有助于疫苗能量稳定释放，最后将做成喷雾剂，通过鼻腔黏膜作用于口腔发挥作用。樊明文18日宣布这一消息时，立即引起众多媒体的关注。 据了解，1983年，樊明文从加拿大回国。当时，免疫防龋的研究在国内尚属空白，而他克服重重困难从被动免疫及蛋白质疫苗、亚单位疫苗、多肽疫苗等主动免疫，到构建靶向定位融合DNA防龋疫苗，同时确立了鼻黏膜免疫途径，而后又将小动物实验过渡到灵长目动物实验，并一步步取得成功。 目前，樊教授带领的课题组，已完成防龋DNA疫苗的构建、组装、动物实验等一系列工作，疫苗临床试验前的工作基本完成。如果在我有生之年无法完成全部的心愿，那么我希望看到龋齿疫苗能上市推广，所有的孩子不再有蛀牙。谈及自己20多年的研究心血时，樊明文充满信心。 樊明文说，儿童期是人一生中龋病的易感期，只要抓好这一阶段，龋病完全可得到控制。变形链球菌是造成龋齿的主要病因，在儿童1至3岁变形链球菌吸收定植前使用，可以发挥疫苗的防龋作用。不过，考虑到儿童使用疫苗的安全性等多种因素，疫苗的面市还有比较长的路要走。 龋齿也称龋病，俗称蛀牙或虫牙，其特点是牙齿硬组织在色、形、质等方面均发生变化。世界卫生组织提出，龋齿是继癌症、心血管疾病后，第三位危害人类健康的非传染性疾病。资料显示，我国5岁儿童龋齿率在64%，35-44岁的成年人更高，达到88%，而65-74岁的老年人则高达98.4%。龋齿的防治已成为备受关注的公共卫生问题。 龋病可直接危及心脏 很多人认为，蛀牙只是小毛病，不过影响人们的咀嚼。实际上，它与人体的许多器官有关，最为直接的是影响人的心脏。专家研究发现，许多死亡率高的疾病，如心脏病、肾病、关节炎等，都可能由龋病引起，预防龋齿已成为世界医学专家共同关注的热点问题。 对于这一世界性难题，国外较早开展对策。如美国政府推行自来水中加氟等措施，现已取得非常好的效果。然而，自来水中，0.8ppm（百万分之一单位）的氟含量是防龋的最佳安全值，但我国地理条件复杂，比如贵州等地区，含氟量就高达10ppm，因此不能统一推行这一措施。 目前，在市面上，防蛀市场上主要有4类产品：一种是含氟制剂，如含氟牙膏，其防龋原理为促进牙齿钙化，减少酸性腐蚀，有一定效果；二是含抗菌药物的漱口液，但因其广谱灭菌、耐药性等副作用，应用受到限制；三是由植物提取物制成的防龋成分，如含中药提取物的牙膏、漱口液、口胶片等，有一定防治龋齿作用，但其为药物，不宜长期使用；四是目前市场上被广泛使用的木糖醇，木糖醇作为代糖取代蔗糖，不被细菌利用产酸，减少酸性物质的产生，但它并不能抑制清除致龋细菌，无法从根本上解决防龋护齿的实质性问题。 樊明文教授指出，含氟牙膏是目前公认的最有效的防龋方式，但也一直存在争议。如儿童刷牙容易误服牙膏残液，过量地摄入氟，会严重影响儿童骨骼的生长发育，引起急性氟中毒。 免疫防龋开启中国模式 由武大医学院开展的免疫防龋，则为防龋打开了一条全新的通道，这一研究已走在世界前列。 早在上世纪80年代，武大医学院就肩负国家重托，开展了免疫防龋攻关并为之倾注了大量心血。随着科研难题的逐渐破解，武汉大学医学院的研究人员构建防龋的DNA疫苗，成功地减少了变形链球菌在悉生动物中引起的各级龋齿，今年初，这一研究成果，已经公布在世界著名的 Journal of Dental Research 杂志上。 据樊教授介绍，变形链球菌是引发龋齿和牙周炎等疾病的罪魁祸首，科研人员正是针对变形链球菌研发出了抗龋齿免疫球蛋白抗体，这种蛋白抗体可与变形链球菌表面抗原进行特异性的结合，直接抑制细菌，使其丧失对牙齿的黏附和腐蚀能力，从而达到针对性的防龋齿的效果。 防龋疫苗的问世将为世界医学的进步带来重大影响。目前，防龋齿疫苗即将进入临床试验阶段，可取代含氟制剂安全地预防龋齿。将来，如果防龋疫苗一旦上市，全国推广防龋疫苗必将成为最佳选择。 动物实验可降低70% 我们在动物身上实验结果表示，接种DNA防龋疫苗后，患龋齿率至少下降了60%，如果用在人身上，至少应该可以让患龋率下降30%。樊教授十分谦虚地说。 对于DNA防龋疫苗的直接作用，记者昨晚联系到樊明文教授的助手张宇红博士。她告诉记者，2007年10月，课组已申请到国家的支撑计划，目前武大口腔医学院、华中科技大学生命科学院、武汉生物研究所、中科院病毒研究所等四个单位已开始联合生产出这一疫苗，目前疫苗已在小鼠、大鼠、兔、猴等大批动物上做完了实验，实验结果表明，效果十分显著，患龋率下降70%左右。但目前我国对于食品药品的安全性管理十分严格，目前疫苗还没有做人的实验，我们必须拿到国家相关的批文才可以进行，但相信，这一疫苗在人体上身的效果不会很差！张宇红博士说。 将来就像打乙肝疫苗 据介绍，目前，DNA防龋疫苗已从实验室试验转入规范的工厂进行试验，包括测试疫苗的毒性等。对于这项即将破壳而出的科研成果，樊明文教授十分看重，因为他为此注入大量的心血，就像对待自己的孩子。18日，他用愉快的口吻说：用于人体的龋齿疫苗一旦上市，口腔医学就向前迈进了一大步！ 樊教授称，目前武大口腔医学院专家正在研制的疫苗，适合1-3岁的儿童，使用途径是向鼻腔内的粘膜直接喷雾，易被孩子和家长接受，这个疫苗成本不高，可以被普通家庭接受。如果试验效果很好，不排除这个疫苗可以像儿童注射乙肝的疫苗一样，成为我国政府的一项公益行为，龋齿疫苗的效果可持续数年。 事实上，儿童期是人一生中龋病的易感期，只要抓好这一阶段，龋病完全可得到控制；当然，专家也指出，龋齿疫苗的效果不可能达到100%，造成龋齿的因素很多，防龋工作还需多管齐下。 樊明文 姓 名：樊明文 性 别：男 出生年月：1939年4月 民 族：汉 籍 贯：湖北 毕业院校：四川大学华西口腔医学院 (原华西医科大学口腔系) 研究专业：口腔内科学 研究领域：龋病学、口腔生物学 兼职情况 中华口腔医学会副会长 湖北省医学会副会长 国务院学位委员会口腔学科评议组召集人 人民卫生出版社口腔医学教材编审委员会主任委员 国际牙科研究协会中国分会执行主席 国际牙科研究协会地区发展委员会委员 学术荣誉和荣誉称号 1991年起为国家级政府特殊津贴获得者 1992年被评为湖北省省管专家 1993年被评为湖北省有突出贡献中青年专家 1994年被评为国家级有突出贡献专家 1994年被评为全国省级医院优秀院长 1998年当选为第九届全国政协委员 2003年被评为武汉大学十大教学名师 在研科研项目: 项目名称 项目来源 起止时间 科研经费(万元) 成人牙髓干细胞的鉴定、分化特征及诱导牙髓再生的研究 教育部博士点基金 2002~2005 5 龋病预防和治疗的分子机制研究 武汉大学科创基金 2002~2005 8 DNA防龋疫苗及免疫防龋制剂研制及开发 省科技攻关计划 2002~2005 20 靶向融合防龋DNA疫苗的研制和粘膜免疫防龋的作用机制 国家自然科学基金面上项目 2002~2005 20 被动免疫防龋生物制品特异性鸡蛋黄抗体喷雾 省科技攻关计划 2003~2005 5 靶向DNA疫苗激发粘膜免疫反应机制的研究 国家自然科学基金重点项目 2003~2006 120 中草药活性成份预防口腔疾病 省教委基金 2002~2005 6 靶向融合防龋DNA疫苗的临床前研究和开发 武汉市科技攻关计划 2006-2008 8 代表性论文 : Jia Rong , Guo Jihua , Fan Mingwen* , Bian Zhuan , Chen Zhi , Fan Bing , Yu Fei, Xu Qingan . Immunogenicity of CTLA4 fusion anti-caries DNA vaccine in rabbits and monkeys. Vaccine , 2006 ;24:5192-5200 Shen Jing, Fan Mingwen*, Chen Xinming, Wang Shuozhi,Wang Li, Li Yuan. Glandular Odontogenic Cyst in China:Report of 12 Cases and Immunohistochemical Study. J Oral Pathology Medicine 2006, 35:175-82 Xu Qiong, Fan Mingwen*, Bing Fan , GSP Cheung , Hanlin Hu. A new quantitative method using glucose for analysis of endodontic leakage. Oral Surgery Oral Medicine Oral Pathology Oral Radiology Endodonitics 2005; 99:107-111 Xu Qingan , Yu Fei , Fan Mingwen* , Bian Zhuan , Guo Jihua , Jia Rong ,. Chen Zhi , Peng Bin , Fan Bing . 2005 . Immunogenicity and protective efficacy of a targeted fusion DNA construct against dental caries . Caries Research 2005;39:422-431 Xue Jingling, Fan Mingwen*, Wang Shuozhi, Chen Xinming, Li Yuan, Wang Li. A clinical study of 674 patients with oral lichen planus in China. Journal of Oral Pathology Medicine 2005;34 (8): 467-472 Li Yuhong, Fan Mingwen*, Bian Zhuan, Chen Zhi, Peng Bing, Guo Jihua .Chitosan microparticles intended for anti-caries DNA vaccine mucosal delivery: synthesis, characterization and transfection. J Wuhan University of Technology, Materials Science Edition.2005;20(2):35-38 Li Yuhong, Fan Mingwen*, Bian Zhuan, Chen Zhi, Zhang Qi, Yang HR.Chitosan-DNA microparticles as mucosal delivery system: synthesis, release and distribution. Chinese Medical Journal .2005; 118 (11):936-941 Bing Fan, Gary S. P. Cheung, Mingwen Fan*, James L. Gutmann, Zhuan Bian. C-shaped Canal System in Mandibular Second Molars: Part-IAnatomical Features. Jounal of Endodontics 2004;30:899-903 Bing Fan, Gary S. P. Cheung, Mingwen Fan*, James L. Gutmann and Wei Fan. C-shaped Canal System in Mandibular Second Molars: Part-IIRadiographic Feature. Jounal of Endodontics 2004;30:904-908 Rong Jia, Jihua Guo, Mingwen Fan*, Zhuan Bian, Zhi Chen, Bin Peng, Bing Fan. Mucosal immunization against dental caries with plasmid DNA encoding pac gene of Streptococcus mutans in rats. Vaccine 2004;22 25112516 Guo JH, Jia R, Fan MW*, Bian Z, Chen Z, Peng B..Construction and immunogenic characterization of a fusion anti-caries DNA vaccine against PAc and 2glucosyltransferase I of Streptococcus mutans . Journal of Dental Research 2004 ;83 (3): 266-270 Hongkun Wu, Mingwen Fan*, Xuedong Zhou, Anchun Mo, Zhuan Bian, Qi Zhang, Zhi Chen. Detection of Streptococcus mutans and Streptococcus sobrinus on the Permanent First Molars of the Mosuo People in China. Caries Research 2003;37:374-380 Mingwen. Fan*, Zhuan. Bian, Zhixiang. Peng, Yan. Zhong, Zhi. Chen, Bin. Peng, and Rong. Jia. A DNA Vaccine Encoding a Cell-surface Protein Antigen of Streptococcus mutans Protects Gnotobiotic Rats from Caries. J Dent Res 2002;81(11):784-787 Min Nie, Mingwen Fan*, Zhuan Bian. Transmission of mutans streptococci in adults within Chinese population. Caries Research. 2002;36(3):161-166 信息分析平台： http://www.gopubmed.org/web/gopubmed/WEB10O00d000j100300.y 检索策略：anti-caries and DNA vaccine 相关文献计量分析结果： Top Years Publications 2009 5 2006 5 2007 3 2004 3 2002 3 2008 2 2003 2 2001 1 Top Countries Publications China 24 Top Cities Publications Wuhan 19 Jinan 2 Zunyi 1 Chengdu 1 Top Journals Publications Vaccine 6 Zhonghua Kou Qiang Yi Xue Za Zhi 5 J Dent Res 4 J Gene Med 3 Hua Xi Kou Qiang Yi Xue Za Zhi 3 Shanghai Kou Qiang Yi Xue 2 Acta Pharmacol Sin 1 1 2 3 ... 14 Top Terms Publications Vaccines 24 Vaccination 24 DNA 24 Vaccines, DNA 23 Streptococcus mutans 20 Dental Caries 18 Immunization 18 Animals 18 Immunity 16 Streptococcus 15 Plasmids 15 Proteins 13 immune response 12 Antigens 12 Antibodies 12 antigen binding 12 Glucosyltransferases 11 Immunoglobulin G 11 Streptococcal Vaccines 11 Genes 11 1 2 3 ... 14 1 2 3 4 Top Authors Publications Fan M 13 Jia R 12 Chen Z 11 Guo J 11 Bian Z 11 Yu F 6 Peng B 6 Xue Q 5 Fan B 3 Li Y 2 Liu C 2 Wang X 2 Jiang G 2 Wu Q 2 Jiang P 2 Liu T 2 Niu Y 1 Sun J 1 Fan M 1 Xu Q 1 1 2 3 4 相关研究报道： Title: Enhanced immunogenicity of an anti-caries vaccine encoding a cell-surface protein antigen of Streptococcus mutans by intranasal DNA prime-protein boost immunization. PMID: 19718694 Related Articles Authors: Li, Y , et.al. Journal: J Gene Med , 2009 Snippet: CONCLUSIONS: The results obtained in the present study suggest that the intranasal DNA prime-protein boost vaccination regimen is a novel strategy for the practical application of DNA vaccine against dental caries. Affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Hubei , China . Title: Construction of a new fusion anti-caries DNA vaccine . PMID: 19493890 Related Articles Authors: Niu, Y , et.al. Journal: J Dent Res , Vol. 88 (5): 455-60 , 2009 Snippet: A fusion anti-caries DNA vaccine , pGJA-P/ VAX , encoding two important antigenic domains, PAc and GLU, of S. mutans, was successful in reducing the levels of dental caries caused by S. mutans in gnotobiotic animals. Affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School Hospital of Stomatology, Wuhan University, 237 Luoyu Road, 430079 Wuhan , Hubei , China . Title: Protective efficacy of two new anti-caries DNA vaccines . PMID: 19446592 Related Articles Authors: Sun, J , et.al. Journal: Vaccine , 2009 Snippet: In this study, we evaluate the potential of the catalytic region to enhance the immunogenicity of the anti-caries DNA vaccine . Affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School Hospital of Stomatology, Wuhan University, 237 Luoyu Road, 430079 Wuhan , Hubei , China . Title: Mucosal and systemic immunization with targeted fusion anti-caries DNA plasmid in young rats. PMID: 19428904 Related Articles Authors: Liu, G X , et.al. Journal: Vaccine , Vol. 27 (22): 2940-7 , 2009 Snippet: Our group had previously reported that a plasmid DNA vaccine pGJA-P/VAX against the glucosyltransferase ( GTF ) enzyme and cell surface antigen AgI /II ( PAc ) of Streptococcus mutans (S. mutans) elicited a specific and protective immunity in adult experimental animal models. Affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School Hospital of Stomatology, Wuhan University, Wuhan , Hubei , China . Title: Analysis of the molecular mechanisms of targeted anti-caries DNA plasmid enhancing antibody responses by gene arrays. PMID: 19248140 Related Articles Authors: Xu, Q A , et.al. Journal: J Gene Med , Vol. 11 (4): 354-60 , 2009 Snippet: Studies have shown that CTLA4 targeted DNA vaccines induced accelerated and increased antibody responses compared to nontargeted vaccines . Affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Hubei , China . Title: Effects of targeted fusion anti-caries DNA vaccine pGJA-P/VAX in rats with caries. PMID: 18789994 Related Articles Authors: Liu, C , et.al. Journal: Vaccine , Vol. 26 (51): 6685-9 , 2008 Snippet: Our previously prophylactic studies have proved that the anti-caries DNA vaccine pGJA-P/VAX could generate effective immune response by intramuscular (i.m.) and intranasal (i.n.) administration in rats without caries. Affiliation: Key Laboratory for Oral Biomedical Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Luoyu Road 237, 430079 Wuhan , Hubei , China . Title: Biodistribution and expression of targeted fusion anti-caries DNA vaccine pGJA-P/VAX in mice. PMID: 18085725 Related Articles Authors: Liu, C , et.al. Journal: J Gene Med , Vol. 10 (3): 298-305 , 2008 Snippet: OBJECTIVE: To study the biodistribution and expression of anti-caries DNA vaccine pGJA-P/VAX in mice models following intranasal (i.n.) and intramuscular (i.m.) immunization. Affiliation: Key Laboratory for Oral Biomedical Engineering Ministry of Education, School and Hospital of Stomatology, Wuhan University, Luoyu Road 237, 430079 Wuhan , Hubei , China . Title: Enhanced efficacy of CTLA-4 fusion anti-caries DNA vaccines in gnotobiotic hamsters. PMID: 17640488 Related Articles Authors: Zhang, F , et.al. Journal: Acta Pharmacol Sin , Vol. 28 (8): 1236-42 , 2007 Snippet: AIM: To evaluate the comparative immunogenicity and protective efficacy of the cytotoxic T-lymphocyte-associated antigen 4 ( CTLA-4 ) fusion anti-caries DNA vaccines pGJA-P/ VAX1 , pGJA-P, and non-fusion anti-caries DNA construct pGLUA-P in hamsters. Affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School and Hospital of Stomatology, Wuhan University, Wuhan , China . Title: PMID: 17546391 Related Articles Authors: Wang, X H , et.al. Journal: Shanghai Kou Qiang Yi Xue , Vol. 16 (2): 192-5 , 2007 Snippet: PURPOSE: The aim of the study is to construct an anti-caries DNA vaccine with high immunogenicity due to its unique properties of being able to express target antigens both in eukaryotic and prokaryotic host cells and harboring two main virulence genes from caries pathogen Streptoccocus mutans (S. mutans). Affiliation: School of Dentistry, Shandong University, Jinan 250012, Shandong Province, China . wangxiaohua@mail.sdu.edu.cn Title: Protective efficacy of a targeted anti-caries DNA plasmid against cariogenic bacteria infections. PMID: 17095128 Related Articles Authors: Xue, Q A , et.al. Journal: Vaccine , Vol. 25 (7): 1191-5 , 2007 Snippet: We have previously reported that a targeted anti-caries DNA plasmid pGJA-P/ VAX which was constructed against the antigenic determinants of Streptococcus mutans (S. mutans) successfully induced antibody responses in mice and monkeys. Affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, Schoolhospital of Stomatology, Wuhan University, Luoyu Road 237, 430079 Wuhan , Hubei , China . Title: PMID: 16999363 Related Articles Authors: He, K L , et.al. Journal: Hua Xi Kou Qiang Yi Xue Za Zhi , Vol. 24 (4): 370-3 , 2006 Snippet: OBJECTIVE: To analysis the homology among the extended-V region of the surface proteins in different serotype Streptococcus mutans (c, f, d, g) and to find out it's significance in anti-caries vaccine . Affiliation: Dept. of Oral Medicine, Stomatological Hospital of Zunyi Medical College, Zunyi 563003, China . Title: Immunogenicity and persistence of a targeted anti-caries DNA vaccine . PMID: 16998131 Related Articles Authors: Xue, Q A , et.al. Journal: J Dent Res , Vol. 85 (10): 915-8 , 2006 Snippet: We have previously reported that a targeted anti-caries DNA vaccine , pGJA-P, induced accelerated and increased antibody responses compared with a non-targeted anti-caries DNA vaccine . Affiliation: The Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School Hospital of Stomatology, Wuhan University, Luoyu Road 237, 430079 Wuhan , Hubei , China . Title: PMID: 16862366 Related Articles Authors: Wang, X H , et.al. Journal: Shanghai Kou Qiang Yi Xue , Vol. 15 (3): 294-7 , 2006 Snippet: CONCLUSION: The results showed that the expressing plasmid carrying the GBR gene was constructed successfully and the purified recombinant GBR protein can elicit specific murine system immune response, which is necessary for further experiments including construction of bivalent anti-caries DNA vaccine and studies both in vitro and in vivo. Affiliation: School of Stomatology, Shandong University, Jinan 250012, Shandong Province, China . Title: PMID: 16784605 Related Articles Authors: Guo, J H , et.al. Journal: Zhonghua Kou Qiang Yi Xue Za Zhi , Vol. 41 (5): 272-4 , 2006 Snippet: The size of antigen may affect the expression level of CTLA-4 targeted anti-caries DNA vaccine . Affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School of Stomatology, Wuhan University, Wuhan 430079, China . Title: Immunogenicity of CTLA4 fusion anti-caries DNA vaccine in rabbits and monkeys. PMID: 16675075 Related Articles Authors: Jia, R Q , et.al. Journal: Vaccine , Vol. 24 (24): 5192-200 , 2006 Snippet: Here, we show anti-caries DNA vaccines , pGJA-P and pGJA-P/ VAX , encoding Streptococcus mutans antigens fused to cytotoxic T lymphocyte antigen-4 ( CTLA4 ), which binds to B7 molecule expressed on the surfaces of antigen-presenting cells. Affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School Hospital of Stomatology, Wuhan University, 237 Luoyu Road, Wuhan 430079, PR China . Title: PMID: 15196400 Related Articles Authors: Jia, R Q , et.al. Journal: Zhonghua Kou Qiang Yi Xue Za Zhi , Vol. 39 (3): 248-51 , 2004 Snippet: OBJECTIVE: To detect the immunoreactivity of targeted fusion anti-caries DNA vaccine pGJA-P in vitro, and the ability to enhance the immune responses compared with the non-targeted fusion anti-caries DNA vaccine pGLUA-P. Affiliation: Key Lab for Oral Biomedical Engineering of Ministry of Education, School of Stomatology, Wuhan University, Wuhan 430079, China . Title: Mucosal immunization against dental caries with plasmid DNA encoding pac gene of Streptococcus mutans in rats. PMID: 15193375 Related Articles Authors: Jia, R Q , et.al. Journal: Vaccine , Vol. 22 (20): 2511-6 , 2004 Snippet: By immunizing rats with an anti-caries DNA vaccine , pCIA-P, via different mucosal routes, we found that intranasal (i.n.) immunization with pCIA-P/bupivacaine DNA complexes elicited the highest specific anti-S. mutans saliva S- IgA mucosal antibody responses compared with naked DNA and other routes. Affiliation: Key Laboratory for Oral Biomedical Engineering of Ministry of Education, School Hospital of Stomatology, Wuhan University, Wuhan 430079, PR China . Title: Construction and immunogenic characterization of a fusion anti-caries DNA vaccine against PAc and glucosyltransferase I of Streptococcus mutans. PMID: 14981132 Related Articles Authors: Guo, J H , et.al. Journal: J Dent Res , Vol. 83 (3): 266-70 , 2004 Snippet: To develop a highly efficient vaccine against caries, we constructed a fusion DNA vaccine , pGLUA-P, by cloning the GLU region of GTF into a DNA vaccine , pCIA-P, which encodes two highly conservative regions of PAc. Affiliation: Key Lab. for Oral Biomedical Engineering of Ministry of Education, School Hospital of Stomatology, Wuhan University, Wuhan 430079, PR China . Title: PMID: 12930659 Related Articles Authors: Guo, J H , et.al. Journal: Zhonghua Kou Qiang Yi Xue Za Zhi , Vol. 38 (4): 282-4 , 2003 Snippet: OBJECTIVE: To construct and detect the targeted anti-caries fusion DNA vaccine pGJA-P encoding the A-P fragment of pac, glu fragment of gtfB and extracellular region of the human CTLA4 and the Fc region of human Iggamma(1) gene for the targeting antigen to APC . Affiliation: Key Laboratory for Oral Biomedical Engineering Ministry of Education, School of Stomatology, Wuhan University, Wuhan 430079, China . Title: PMID: 12898772 Related Articles Authors: Yang, J , et.al. Journal: Hua Xi Kou Qiang Yi Xue Za Zhi , Vol. 21 (3): 228-30 , 2003 Snippet: The purpose of this study was to examine the potential of anti-caries DNA vaccine pcDNA3-gtfB integrating into the host cell genome. Affiliation: Key Lab. for Oral Biomedical Engineering Ministry of Education, West China College of Stomatology, Sichuan University, Chengdu 610041, China . Title: PMID: 12641963 Related Articles Authors: Jia, R Q , et.al. Journal: Zhonghua Kou Qiang Yi Xue Za Zhi , Vol. 37 (6): 456-8 , 2002 Snippet: OBJECTIVE: To construct a fusion anti-caries DNA vaccine pGLUA-P carrying GLU fragment from gtfB gene of Streptococcus mutans GS-5 and A-P fragment including the A region and P region of PAc protein from a DNA anti-caries vaccine pCIA-P, and to investigate its expression in prokaryotic and eukaryotic cells. Affiliation: Department of Endodontics, School of Stomatology, Wuhan University, Wuhan 430079, China . Title: PMID: 12641962 Related Articles Authors: Guo, J H , et.al. Journal: Zhonghua Kou Qiang Yi Xue Za Zhi , Vol. 37 (6): 452-5 , 2002 Snippet: RESULTS: As for the antibody reactions, there were significantly (P 0.01) differences between rats immunized with DNA vaccine and non-immunized rats. Affiliation: Department of Operative and Endodontics, School of Stomatology, Wuhan University, Wuhan 430079, China . Title: PMID: 12539734 Related Articles Authors: Yang, J , et.al. Journal: Hua Xi Kou Qiang Yi Xue Za Zhi , Vol. 19 (4): 249-52 , 2001 Snippet: It was suggested that recombined plasmid pcDNA3- gtfB had high immune antigenicity and immune responsiveness, and this supported its use as gene vaccine candidates in the development of anti-caries vaccines . Affiliation: College of Stomatology, West China University of Medical Sciences. Title: A DNA vaccine encoding a cell-surface protein antigen of Streptococcus mutans protects gnotobiotic rats from caries. PMID: 12407095 Related Articles Authors: Fan, M W , et.al. Journal: J Dent Res , Vol. 81 (11): 784-7 , 2002 Snippet: To develop vaccines against dental caries, we constructed a DNA vaccine , pCIA-P, which encodes two high-conservative regions of PAc . Affiliation: School of Stomatology, Wuhan University, People's Republic of China . kqyywjtx@public.wh.hb.cn
http://www.sciencenet.cn/htmlpaper/20099151125375627282.shtm 纳米颗粒是否致肺纤维化研究 7名在同一间印厂工作的女工因为胸腔积液、肺纤维化和肉芽肿住院，2名女工在两年内死亡。经过临床和病理检查，凶手并非一般化学污染物，竟可能是纳米颗粒！北京朝阳医院的研究者日前在《欧洲呼吸病学杂志》（ Eur Respir J 2009，34（3）：559）上发表了相关研究。 纳米技术已经越过了科学幻想的边界，成为现实。新兴的纳米颗粒正被越来越广泛地应用于材料、医药、工业等各个行业，将人类的触角伸进了微观世界。纳米纤维、纳米给药系统、纳米涂料，甚至防晒产品中都有纳米技术的脚印。纳米技术在给人们带来无限可能的欣喜时，也引出一个新的问题纳米微粒的尺寸小于自然分子，意味着其完全能够穿过人体的天然屏障，这是否会对人体造成危害？ 一些动物试验证实，小鼠气管接触纳米碳颗粒后，可发生炎症和肺纤维化症状，但在人类研究中尚无此类报道。 独特的病理表现 2007年1月-2008年4月，7名曾在同一家印厂工作的女工因为同样的症状到北京朝阳医院就诊，其临床症状均包括气短、胸腔积液、心包积液等。 入院临床检查发现，这些患者均有单核细胞增多、中性粒细胞减少现象，部分患者的红细胞沉降率升高现象，1例患者血小板减少。经过7个月的随访，6例患者出现低蛋白血症，部分患者还出现谷丙转氨酶、天冬氨酸转氨酶升高。肺活量检测发现，全部患者都有小气道受损、通气功能受限。3例患者有严重肺损伤：最大肺活量（实际值与预测值比例，下同）为24.8%~35.4%；用力肺活量（FVC）为24.6%~35.1%；1秒钟用力呼气容积（FEV1）为24.8%~36.5%。其他4例患者肺损伤程度分别为轻度至中度。 免疫检测和病因学检测排除了病毒性肺炎和肿瘤的可能，2例患者有肺炎支原体或衣原体感染，但与其临床表现不相关。 胸部X线检查和CT检查显示，所有患者都有胸腔积液，5例患者有心包积液，4例患者肺部弥漫性磨玻璃阴影，6例患者肺间质结节，3例患者淋巴结肿大。所有患者都有间质性肺炎和肺纤维化。7个月后，2例患者的间质性肺纤维化快速进展，1例患者出现胸腔钙化。18个月和21个月时，2例患者先后死亡。 病因初现肺部疑有纳米颗粒 什么原因导致了上述病理改变？经过询问，这些患者具备以下共性：她们都曾在同一间印厂工作，同样在没有保护措施的情况下，接触含有纳米颗粒的聚丙烯酸酯达5~13个月；她们在接触后同样的时间范围内出现了相似的症状气短、胸腔积液和心包积液；病理检查结果同样为非特异性肺炎、炎症浸润、肺纤维化和胸腔外源性肉芽肿。研究者因此假设，她们可能接触了同一类型的毒性物质。 进一步检查发现，在这些女工的工作场所、支气管肺泡灌洗液、胸水和肺活检组织中均找到直径为30 nm的颗粒（图1-4）。在电镜下观察到，这些颗粒分布在肺上皮和间皮细胞的胞浆和核质中。肺上皮细胞蜷缩，呈现凋亡形态（图5）。通过检查，所有病例都排除了感染、恶性肿瘤、免疫相关疾病等的可能性。 考虑到患者的病理改变与动物接触纳米物质后的相似，而且在患者的支气管、肺部组织中都找到纳米颗粒物质，因此推测，这些患者的疾病表现和病理改变可能与印厂内的纳米颗粒相关。 图3 18个月后胸腔膜病理检查结果 图4 18个月后肺部病理检查结果 患者就诊时检查显示，肺泡腔内可见到吞噬细胞聚集，肺泡隔增宽、水肿（图1）；胸腔内有外源性肉芽肿，内有纤维蛋白细胞，胸腔积液中有炎性细胞，箭头处指示巨大外源性多核细胞（图2）；18个月后，胸腔膜纤维增厚、肿胀，成纤维细胞增殖，有纤维素样渗出和淋巴细胞聚集（图3）；肺泡隔增厚、血管扩张，充血，肺泡部分呈肺气肿样，伴多核巨细胞散在（图4）。 图5 电镜下观察胸腔积液结果 图5a箭头显示在胸腔积液中，有直径约30 nm的纳米颗粒散在，被纤维化结构包裹，可能是胸腔积液内细胞裂解所致；图5b显示纳米颗粒簇在肺上皮细胞的核质中存在；图5c显示核质中有纳米颗粒的肺上皮细胞，其染色质凝集、缩小，呈新月状，细胞形态特征如同处在凋亡状态；图5d为图5c中部分放大后的结果，图中可见纳米颗粒簇。（以上图片来自研究原文） 纳米颗粒有毒？ 研究者之一、北京朝阳医院职业医学、临床毒理和病理学部的宋玉果医师指出，该研究从临床、病理检查的结果和相关的背景调查推断，这些患者的肺损害可能是缘于存在于印厂聚丙烯酸酯中的纳米颗粒。但因为印厂已经关闭，他们始终未能找到肇事印料的准确成分，因而也未能定量计算这些患者纳米颗粒的暴露水平。这些都为人们留下了一个未解的谜题。 对于这样的结果，美国华盛顿伍德罗威尔逊（Woodrow Wilson）国际中心的纳米技术专家梅尼亚德（Maynard）说，这些患者的病理损害集中在肺内，与动物受纳米颗粒刺激后的病理表现相似，因此这样的损害不像是更大颗粒造成的。但因为研究者并未找出哪种纳米颗粒造成了这样的肺部损害，以及造成损害的纳米颗粒浓度，因此不能确定这样的病理改变是由于纳米颗粒所致，还是多种因素共同作用的结果。不过，人们应该研究接触纳米材料的工作者可能面临的职业暴露危险，并找出必要的防护措施。 英国爱丁堡大学的呼吸毒理学家唐纳森（Donaldson）以及英国阿伯丁大学环境和职业医学专家西顿（Seaton）教授对上述结果持怀疑态度。他们认为，仅凭现有的证据不能证明纳米颗粒和疾病之间的因果关系，应该考虑到患者之前的作业环境，可能的职业暴露因素等。患者的症状和病理表现都与化学物质毒性有关，虽然纳米颗粒存在于肺组织中，但这并不意味着纳米颗粒是始作俑者。（来源：中国医学论坛报 阿信） 更多阅读 《欧洲呼吸病学杂志》发表论文摘要（英文） 《自然》相关报道（英文） http://erj.ersjournals.com/cgi/content/abstract/34/3/559 Published online before print August 20, 2009, 10.1183/09031936.00178308 This Article Full Text Full Text (PDF) Supplementary figures All Versions of this Article: 34/3/559 most recent 09031936.00178308v1 Alert me when this article is cited Alert me if a correction is posted Permissions Request Permissions Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Song, Y. Articles by Du, X. PubMed PubMed Citation Articles by Song, Y. Articles by Du, X. Eur Respir J 2009; 34:559-567 Copyright ERS Journals Ltd 2009 Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma Y. Song 1 , X. Li 2 and X. Du 1 Depts of 1 Occupational Medicine and Clinical Toxicology, and 2 Pathology, Beijing Chaoyang Hospital, Capital University of Medical Sciences, Beijing, China. CORRESPONDENCE: Y. Song, Dept of Occupational Medicine and Clinical Toxicology, Beijing Chaoyang Hospital, No. 8, Baijiazhuang Road, Chaoyang District, Beijing, China (100020). E-mail: songrain123@hotmail.com
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